AIDS is a global pandemic with over 20 million HIV-infected individuals worldwide. A major focus within our laboratory has been defining the unique epidemiologic, clinical, virologic and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In Pune, India, we established a prospective cohort of over 3,000 high-risk individuals attending STD clinics, of whom 21% were seropositive for HIV-1. The HIV incidence was 10.2% with rates as high as 28% for commercial sex workers. Recurrent genital ulcers and non-ulcerative STDs were independently associated with a 7 and 3- fold increased risk of HIV seroconversion, respectively. Genetic analysis of viral strains demonstrated clade C2 and C3. A community-based STD mass treatment campaign among 5,000 individuals in Uganda resulted in a 60% reduction in the prevalence and incidence of bacterial STDs. In a multi-center study on perinatal transmission in the U.S., we determined that elevated RNA viral levels at birth were suggestive of in utero infection and that a high plasma RNA viral level in the first two months of life was associated with a rapid progression to AIDS or death. In addition, co- infection of the mother with HIV and hepatitis C virus (HCV) resulted in a 3-fold increase in perinatal transmission of HCV and a 2-fold increase in perinatal transmission of HIV. Short-course intermittent chemotherapy for tuberculosis in 427 patients in Haiti resulted in a 94% efficacy rate in HIV seropositive patients and 97.2% rate in HIV seronegative patients. In studies of HIV-1 and HTLV-1 co-infection in Brazil, we documented a higher incidence of myelopathy and peripheral neuropathy among dually infected individuals. In addition, T and B cell responses to pneumococcal and tetanus immunizations were markedly diminished among dually infected individuals compared to these infected with HIV-1 alone. Median serum HIV RNA levels were similar in both co-infected and singly infected patients, suggesting that the advanced neurologic abnormalities in co-infected patients were unrelated to HIV viral level.